Submitted to: Veterinary Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/18/2002
Publication Date: 12/20/2002
Citation: HALLING, S.M. PARADIGM SHIFTS IN VACCINE DEVELOPMENT: LESSONS LEARNED ABOUT ANTIGENICITY, PATHOGENICITY AND VIRULENCE OF BRUCELLAE. VETERINARY MICROBIOLOGY. 2002. v. 90. p. 545-52
Interpretive Summary: The Brucellosis Research Unit, NADC began using molecular biology and recombinant DNA techniques to study the virulence and pathogencity of the causative agent of bovine brucellosis about fifteen years ago. A subunit vaccine and several candidate genetically engineered vaccines were tested in various cell systems, animal models, and the natural host. New information about the virulence and pathogencity of Brucellae which may be useful in the construction of wildlife vaccines have resulted from these studies.
Technical Abstract: As part of a program to support the USDA Animal Plant Health Inspection Service Bovine Brucellosis Eradication Program, the Brucellosis Research Unit of the National Animal Disease Center (NADC) sought to develop of a bovine brucellosis vaccine that would allow vaccinated animals to be distinguished from virulent field infected animals. In order to meet that goal, several avenues of research were undertaken to construct and test candidate vaccines, including B. abortus RB51. In early vaccine development studies, a subunit preparation obtained by extracting B. abortus with salts was studied as a candidate subunit vaccine. Later, molecular biological techniques were used both to clone genes encoding products found in the salt extract (BCSP31 and Cu-Zn SOD) and genes encoding proteins of B. abortus that were antigenic (HtrA) or possibly essential (two component systems) for full virulence of B. abortus. In vitro systems using mammalian cells lines such as HeLa and macrophage-related were used along with the mouse model and host animal models. Results obtained at NADC and in other Brucellosis research laboratories, using survival in mammalian cell lines and the mouse model to access pathogenicity and virulence of genetically engineered strains, does not always identify loci that are essential for full virulence or pathogenicity in the natural host, the bovine. Studies at NADC and other brucellosis laboratories showed that antigenicity was not a predictor of the effectiveness of a protein as a subunit vaccine.